School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Médical Universitaire (CMU), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Médical Universitaire (CMU), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
Eur J Pharm Biopharm. 2018 Sep;130:128-142. doi: 10.1016/j.ejpb.2018.06.008. Epub 2018 Jun 9.
Immunogenicity assessment of therapeutic proteins is routinely performed through various techniques during the drug development process: (i) in silico to design the least immunogenic protein possible, (ii) in vitro using mainly classic 2D assays with PBMC-derived cells or immune cell lines to follow protein uptake, immune cell maturation and pro-inflammatory cytokines released, (iii) in vitro using 3D models of the human immune lymphatic system or full-thickness skin, (iv) and finally in vivo with preclinical and clinical studies. This review focuses primarily on the immunogenicity assessment of therapeutic proteins injected subcutaneously and new in vitro models that may be used as specific models of this tissue.
(i) 利用计算机设计出免疫原性尽可能低的蛋白质，(ii) 利用主要基于经典二维检测方法，使用 PBMC 来源的细胞或免疫细胞系，以跟踪蛋白摄取、免疫细胞成熟和释放促炎细胞因子，(iii) 利用人免疫淋巴系统或全层皮肤的 3D 模型，(iv) 最后通过临床前和临床研究进行体内评估。本文主要关注皮下注射治疗性蛋白的免疫原性评估，以及可作为该组织特定模型的新型体外模型。
